A 9-year-old female presented to neurology outpatient department of our hospital with complaints of recurrent generalized tonic–clonic seizures since birth and was being treated with anticonvulsants for the same. Patient also had complaints of giddiness and episodes of momentary loss of consciousness. There was history of twitching of left hemiface and eyelid during infancy, often associated with deviation of eyes to the left and groaning. The birth history was unremarkable. Family history revealed no known consanguinity. General examination revealed no dysmorphic features. Neurological examination revealed no cognitive deficits/signs to suggest cerebellar pathology. An electroencephalogram was done in view of her recurrent seizures, which was normal. Initial laboratory work-up was normal. The patient then underwent magnetic resonance imaging (MRI) brain, acquired with a 1.5-T unit (Siemens, Erlangen, Germany). MRI brain revealed hemihypertrophy of left cerebellar hemisphere with disorganized architecture, fissural malorientation with individual folia running vertically rather than horizontally with disorganized foliation, abnormal arborization of white matter predominantly involving mid and dorsal surface of left cerebellar hemisphere and a few suspicious areas of abnormal T2-hyperintense signal in subcortical white matter. Right cerebellar hemisphere and cerebellar vermis were normal. Corpus callosum was normal. Cerebral parenchyma was normal in signal intensity pattern with normal gray–white matter differentiation. Ventricular system was normal (Figures 1 and 2). Cerebellar malformations are uncommon and are usually associated with Dandy–Walker continuum, Joubert syndrome, rhombencephalosynapsis, lissencephaly, Fukuyama congenital muscular dystrophy, Walker–Warburg syndrome, muscle–eye–brain disease, congenital cytomegalovirus infection to name a few.1,2 Isolated unilateral cerebellar hemispheric dysplasia is exceedingly rare with only a few cases previously described in English literature. Cerebellar malformations are less adequately understood entity partly because of the complex cerebellar embryology and limited histologic studies of these disorders. Genes expressed in migration and maintenance of the Purkinje cells and/or in the generation and migration of granular cells when mutated will disrupt cerebellar migration and foliation and thus cause cerebellar malformation.3–5 Cerebellum is known to be a centre for motor learning, coordination, and higher cognitive functions. Clinical presentation of cerebellar malformations is highly variable and depends on the degree of cerebellar involvement, presence of associated cerebral involvement and the underlying disorders such as muscular dystrophy if any. Patel and Barkovich suggested an imaging-based classification of cerebellar malformations and classified the malformations broadly into two types, malformations with cerebellar hypoplasia and the ones with cerebellar dysplasia. Each of these was further classified into focal and diffuse.1 Demaerel gave a classification of abnormalities of cerebellar foliation and fissuration.2 Our index case with disorganized architecture, fissural malorientation and disorganized foliation of left cerebellar hemisphere associated with normal cerebellar vermis, corpus callosum, and absence of cerebral malformation falls into Type 2 category as per the classification by Demaerel.2 Treatment depends upon the severity of symptoms and the underlying disorder in case of syndromic malformations. Generally, treatment is symptomatic and supportive. Understanding of the basics of cerebellar embryology, knowledge of the imaging features, and clinical presentation aids in the precise diagnosis of this disorder and its optimal management.

Creutzfeldt-Jakob disease (CJD) is a fatal neurological illness for which accurate diagnosis is paramount. Real-time quaking-induced conversion (RT-QuIC) is a prion-specific assay with high sensitivity and specificity for CJD. The Canadian endpoint quaking-induced conversion (EP-QuIC) test is similar, but unlike RT-QuIC there is little data regarding its diagnostic utility in clinical practice. In this exploratory predictive value analysis of EP-QuIC in CJD, the negative predictive value (NPV) and positive predictive value (PPV) was 100% and 83%, respectively, with one false-positive result identified. Re-testing this sample with an optimized EP-QuIC protocol eliminated this false-positive result, leading to a PPV of 100%.

Background: Continuous electroencephalographic (cEEG) monitoring is essential to diagnosing non-convulsive seizures (NCS), reported to occur in 7-46% of at-risk critically ill patients. However, cEEG is labour-intensive, and given scarcity of resources at most centres cEEG is feasible in only selected patients. We aim to evaluate the clinical utility of cEEG at our centre in order to optimize further cEEG allocation among critically ill patients. Methods: Using a clinical database, we identified critically ill children who underwent cEEG monitoring in 2016, 2017 and 2018. We abstracted underlying diagnoses, indication for cEEG monitoring, cEEG findings, and associated changes in management. Results: Over this three year period, 928 cEEGs were performed. Among the 100 studies analyzed to date, primary indications for monitoring were characterization of events of unclear etiology (32%), diagnosis of NCS (30%), and monitoring of therapy for seizures (17%). Seizures were captured in 31% of patients (22% subclinical only, 5% electroclinical only, 4% both), which resulted in a treatment change in 90% of cases. Non-epileptic events were captured in 26% of patients. Conclusions: cEEG yielded clinically meaningful information in 57% of cases, frequently resulting in management changes. Subgroup analyses by cEEG indication and ICU location will be presented.

Due to their rareness, it is not known if the clinicopathological features of cerebellar glioblastomas (cGBMs) are different from supratentorial GBMs (sGBMs). We reviewed all 16 cases of cGBMs (total GBMs: 1350) at St. Michael’s Hospital over 18 years and assessed their clinicopathologic features. The mean age at diagnosis was 57 years. The most common presentations were headache (56%) and gait instability (56%). The majority (81%) of cGBMs were hemispheric while 19% involved the midline. There was radiologic evidence of brainstem infiltration at presentation in one case. Radiologically, peritumoral edema (63%) and heterogeneous contrast enhancement (50%) were common. Histologically, cGBM showed leptomeningeal involvement in 10/12 of cases. Uncommon histologic variants included 3 giant cell GBMs, a gliosarcoma, and a tumor with Rosenthal fibres and eosinophilic granular bodies. IDH1 R132H mutation was detected in 3/14 cases, a rate much higher than sGBMs. Additionally, 7/11 tumors had widespread p53 immunopositivity suggestive of TP53 mutation which is in accordance with previous reports in the literature. Of 9 cases tested, none had histone H3 K27M or G34R/V mutation. In summary, cGBMs have unique features that distinguishes them from sGBMs.

Background: Migraine is a prevalent and disabling condition with limited understanding in the developing brain. Adults with chronic migraine show structural alterations in pain and sensory processing regions. Similar data is lacking in children and required for early intervention. Methods: Case-control feasibility study assessing structural brain differences between adolescents with chronic migraine and healthy controls using 3T Siemens structural volumetric MRI analysis. Fifteen subjects with chronic migraine were compared to 25 age and sex matched healthy controls. Non-parametric statistics performed (Kruskal-Wallis). Results: Migraine subjects had reduced volumes in total brain (grey and white matter) (KW p <0.03), total thalamus (KW p <0.01) and hippocampal regions (KW p <0.03). Unilateral (right) cerebellar grey matter volumes were significantly reduced in migraine subjects versus controls (KW p<0.05). No significant differences were found in other regions, including basal ganglia, cortical grey matter and brainstem. Conclusions: Total brain, hippocampal and thalamic volumetric reductions are seen in adolescents with chronic migraine. The regions identified are involved in migraine pathogenesis. This volumetric imaging study should improve understanding of the causes and effects of pediatric migraine.

To explore whether higher degrees of electrophysiological abnormalities are associated with a more frequent exposure to a more aggressive treatment regimen, we performed a retrospective chart review of patients attending the neuromuscular clinic from June 2012 to December 2015 and included 87 patients. We compared treatment regimens during the follow-up period between patients with high and low jitter and decrement. Myasthenia gravis patients with high jitter or decrement at baseline were more frequently treated with intravenous immunoglobulins (IVIG) and/or plasma exchange (PLEX) during the follow-up period. In patients with mild disease, IVIG or PLEX treatment was associated with high decrement.

Second impact syndrome (SIS) is associated with malignant brain swelling and usually occurs in young athletes with one or more prior, recent concussions. SIS is rare and some dispute its existence. We report a case of SIS in Rowan Stringer, age 17, a rugby player who sustained a fatal brain injury despite prompt medical therapy including decompression surgery. The cause of the massive brain swelling was initially unknown. An inquest revealed Rowan’s text messages to friends describing symptoms from two prior, recent rugby brain injuries, likely concussions, within 5 days of the fatal blow and confirming the diagnosis of SIS.

Non-tuberculous mycobacterium encephalitis is rare. Since 2013, a global outbreak of Mycobacterium chimaera infection has been attributed to point-source contamination of heater cooler units used in cardiac surgery. Disseminated M. chimaera infection has presented many unique challenges, including non-specific clinical presentations with delays in diagnosis, and a high mortality rate among predominantly immunocompetent adults. Here, we describe three patients with fatal disseminated Mycobacterium chimaera infection showing initially non-specific, progressively worsening neurocognitive decline, including confusion, delirium, depression and apathy. Autopsy revealed widespread granulomatous encephalitis of the cerebrum, brain stem and spinal cord, along with granulomatous chorioretinitis. Cerebral involvement and differentiation between mycobacterial granulomas and microangiopathic changes can be assessed best on MRI with contrast enhancement. The prognosis of M. chimaera encephalitis appears to be very poor, but might be improved by increased awareness of this new syndrome and timely antimicrobial treatment.

This study assessed whether S-100β protein could be measured in urine when detectable in plasma after a mild traumatic brain injury (mTBI). Clinical data, plasma and urine samples were collected for the 46 adult patients prospectively enrolled in the emergency department (ED) of a Level 1 trauma center. S-100β protein concentrations were analysed using ELISA. S-100β protein was detectable in 91% and 71% of plasma and urine samples, but values were not correlated (r = 0.002). Urine sampling would have been a non-invasive procedure, but it does not appear to be useful in the ED during the acute phase after an mTBI.

Flaviviruses include many viruses causing encephalitis, including West Nile encephalitis, St. Louis encephalitis, tick-borne encephalitis and Japanese encephalitis. Human pegivirus genotype-1 (HPgV-1) is a lesser known member of the Flaviviridae family and has been identified in human serum, cerebrospinal fluid and brain tissue. Here, we describe two adult patients with fatal HPgV-1-associated encephalitis. Neuroimaging revealed multifocal lesions, initially present in the periventricular and brain stem white matter, then one year later throughout the corona radiata bilaterally with marked involvement of the brainstem and cervical spinal cord. Phylogenetic analyses of HPgV-1 showed clustering of brain-derived sequences from both patients with other human pegiviruses. In both patients, a novel 87-nucleotide deletion in the viral NS2 gene was detected. The presence of positive and negative strand HPgV-1 RNA and viral antigens in both patients indicated viral persistence and replication in the CNS. Autopsy showed lymphocyte infiltration and gliosis predominantly in white matter of the brain and brain stem but, to a lesser extent, also in grey matter. Immunofluorescence revealed HPgV-1 NS5A antigen in lymphocytes as well as in astrocytes and oligodendrocytes. Thus, we hypothesize that the novel deletion in the NS2 coding region may have caused HPgV-1 neuroadaptation or might represent a yet unrecognized genotype of human pegivirus.

Guidelines recommend Botulinum toxin-A (BoNT-A) after deep brain stimulation (DBS), although the effectiveness of their combined use is uncertain. A chart review of Parkinson’s disease (17) and dystonia (7) patients undergoing 302 injections with IncobotulinumtoxinA before or after DBS was performed. Patients with cervical dystonia received less IncobotulinumtoxinA after DBS (290.7 ± 124.0 vs. 192.4 ± 131.4, p = 0.005) and experienced an increased benefit (4.0 ± 3.4 vs. 8.4 ± 3.6 weeks, p = 0.003). No significant differences were found when comparing the treatment outcomes of 14 patients who received both IncobotulinumtoxinA and OnabotulinumtoxinA after DBS. The use of BoNT-A after DBS is a useful strategy although prospective studies are needed.

Background: Growing evidence has that a suggested that mental health strongly influences quality of life (QoL) in adolescents with epilepsy. In addition, research has suggested that these mental health issues are associated with increased seizure burden and worsened health outcomes. Despite this, and the elevated rate of mental health issues in this population, seizure control tends to be the dominant or sole concern for treating physicians. Methods: In order to look at potential predictors of QoL in adolescents we looked at seizure related data, demographic variables, and comorbid conditions in 70 adolescents with epilepsy aged 14 to 18 (M= 16.3l; 37 males, 33 females) enrolled into an epilepsy transition clinic. Results: Regression analysis found that mental health remained a significant and independent predictor of QoL even when other significant seizure related variables were accounted for (t(58)= -3.44, p= .001). Furthermore, when looking at the individual subscales of patient QoL (e.g., memory, social support, stigma), mental health was consistently found to be the strongest correlate. Conclusions: These results demonstrate that in order to ensure the best outcomes for transition-aged adolescents with epilepsy, it is important to not only manage and treat seizures, but also to assess and treat mental health issues.